Project Summary The mission of the National Institute on Aging includes elucidation of the causes as well as treatment of all aspects of aging. Age-related hearing loss (ARHL) is one of the most common ailments associated with aging. In fact, the number of people with ARHL exceeds that of any other acquired hearing loss. The prevalence of this aging pathology is a compelling indicator of the need to identify the in-depth mechanisms of ARHL and to provide comprehensive strateties with which the communication disability can be alleviated. The prevailing account suggests that the etiology of ARHL is intrinsic to the neural mechanisms of aging. Neuronal degeneration as a persistent feature of ARHL abounds in archival human temporal bone analyses, providing a compelling rationale for targeting spiral ganglion neurons (SGN). The overall aims of the present application are to investigate the very early, initiating mechanisms of sensorineural ARHL and to propose avenues for restoration of auditory function. The purpose of Core C is to support Projects 1 through 3 in advancing knowledge, at the cellular and molecular neuroscience level in the 8th nerve, its synapses, cells of input in the organ of Corti and cell bodies in Rosenthal?s canal. Core C's mission is to assess age-related ultrastructural changes at the hair cell-SGN synapses, in the SG cell as well as the integrity of the tight junctions in the organ of Corti. Studies of 8th nerve, SGC and HC function conducted in the main Projects are enhanced by high resolution and/or ultrastructural characterizations of the biological specimen. To this end, the Project investigators have access to integrated services of Core C that include a comprehensive range of electron microscopy and imaging techniques. These services include tissue preparation and image acquisition services for structural/ultrastructural analysis as well as ultrastructural localization of proteins in the auditory periphery thus allowing the Project investigators to focus on innovative cellular and molecular analyses of the same tissue. The Core services allow a centralized source for microscopy and digital imaging services. The availability of complex tissue preparation and subsequent staining by a highly qualified electron microscope technician, collaboration with scientists well-versed in freeze-fracture and electron tomography assures consistent data collection using classical and cutting edge technology. The Core Director assures that the most appropriate experimental designs and data analysis have been utilized. Appropriate review of requests for structural analyses assures that there is a fair and equitable distribution of resources among users.